The processes which act in mineral dust source regions and factors which contribute to interannual variability within dust plumes emanating from them are poorly understood. In this case study, we focus on processes modulating emissions of atmospheric mineral aerosols from a large ephemeral lake. We focus on one key ephemeral lake dust source in southern Africa, the Makgadikgadi Pans of Botswana. A range of satellite [for example, Total Ozone Mapping Spectrometer (TOMS), Moderate Resolution Imaging Spectrometer (MODIS)] and climate data (from meteorological stations and reanalysis data sources) are extracted and compared, highlighting initial problems (for example, data quality, calibration, record length) associated with long-term (10–20 years) monitoring of dust with regional sources in this and other dryland regions. Nevertheless, comparisons of satellite-retrieved inundation, mineral aerosols, vegetation abundance, and climate data for the 1980–2000 period suggest that desert dust loadings are intermittently influenced by the extent and frequency of lake inundation, sediment inflows, and surface wind speed variability. In addition, a significant proportion of the observed variability in the dust and hydrological cycle of this source could also be attributed to El Niño-Southern Oscillation (ENSO) and Indian Ocean sea surface temperature anomalies. Both are known to have an important role in modulating rainfall variability in southern Africa.